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Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Author

Listed:
  • Roger D. Kouyos

    (University of Zurich
    University of Zurich)

  • Peter Rusert

    (University of Zurich)

  • Claus Kadelka

    (University of Zurich
    University of Zurich)

  • Michael Huber

    (University of Zurich)

  • Alex Marzel

    (University of Zurich
    University of Zurich)

  • Hanna Ebner

    (University of Zurich)

  • Merle Schanz

    (University of Zurich)

  • Thomas Liechti

    (University of Zurich
    National Institutes of Health)

  • Nikolas Friedrich

    (University of Zurich)

  • Dominique L. Braun

    (University of Zurich
    University of Zurich)

  • Alexandra U. Scherrer

    (University of Zurich
    University of Zurich)

  • Jacqueline Weber

    (University of Zurich)

  • Therese Uhr

    (University of Zurich)

  • Nicolas S. Baumann

    (University of Zurich)

  • Christine Leemann

    (University of Zurich
    University of Zurich)

  • Herbert Kuster

    (University of Zurich
    University of Zurich)

  • Jean-Philippe Chave

    (Clinique de La Source)

  • Matthias Cavassini

    (University of Lausanne)

  • Enos Bernasconi

    (Regional Hospital Lugano)

  • Matthias Hoffmann

    (Cantonal Hospital St. Gallen)

  • Alexandra Calmy

    (University of Geneva)

  • Manuel Battegay

    (University of Basel)

  • Andri Rauch

    (University of Bern)

  • Sabine Yerly

    (University of Geneva)

  • Vincent Aubert

    (University of Lausanne)

  • Thomas Klimkait

    (University of Basel)

  • Jürg Böni

    (University of Zurich)

  • Karin J. Metzner

    (University of Zurich
    University of Zurich)

  • Huldrych F. Günthard

    (University of Zurich
    University of Zurich)

  • Alexandra Trkola

    (University of Zurich)

Abstract

Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines1. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare2, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.

Suggested Citation

  • Roger D. Kouyos & Peter Rusert & Claus Kadelka & Michael Huber & Alex Marzel & Hanna Ebner & Merle Schanz & Thomas Liechti & Nikolas Friedrich & Dominique L. Braun & Alexandra U. Scherrer & Jacqueline, 2018. "Tracing HIV-1 strains that imprint broadly neutralizing antibody responses," Nature, Nature, vol. 561(7723), pages 406-410, September.
    • Handle: RePEc:nat:nature:v:561:y:2018:i:7723:d:10.1038_s41586-018-0517-0
    DOI: 10.1038/s41586-018-0517-0
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